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Journal of Translational Medicine

, 14:241

Immunobiology andimmunotherapy

Abstract

BackgroundTumour resistance to a wide range of drugs multiple drug resistant, MDR acquired after intensive chemotherapy is considered to be the main obstacle of the curative treatment of cancer patients. Recent work has shown that oncolytic viruses demonstrated prominent potential for effective treatment of diverse cancers. Here, we evaluated whether genetically modified vaccinia virus LIVP-GFP may be effective in treatment of cancers displaying MDR phenotype.

MethodsLIVP-GFP replication, transgene expression and cytopathic effects were analysed in human cervical carcinomas KB-3-1 MDR−, KB-8-5 MDR+ and in murine melanoma B-16 MDR−, murine lymphosarcomas RLS and RLS-40 MDR+. To investigate the efficacy of this therapy in vivo, we treated immunocompetent mice bearing murine lymphosarcoma RLS-40 MDR+ 6- to 8-week-old female CBA mice; n = 10-group or melanoma B-16 MDR− 6- to 8-week-old female C57Bl mice; n = 6-group with LIVP-GFP 5 × 10 PFU of virus in 0.1 mL of IMDM immediately and 4 days after tumour implantation.

ResultsWe demonstrated that LIVP-GFP replication was effective in human cervical carcinomas KB-3-1 MDR− and KB-8-5 MDR+ and in murine melanoma B-16 MDR−, whereas active viral production was not detected in murine lymphosarcomas RLS and RLS-40 MDR+. Additionally, it was found that in tumour models in immunocompetent mice under the optimized regimen intratumoural injections of LIVP-GFP significantly inhibited melanoma B16 33 % of mice were with complete response after 90 days and RLS-40 tumour growth fourfold increase in tumour doubling time as well as metastasis.

ConclusionThe anti-tumour activity of LIVP-GFP is a result of direct oncolysis of tumour cells in case of melanoma B-16 because the virus effectively replicates and destroys these cells, and virus-mediated activation of the host immune system followed by immunologically mediated destruction of of tumour cells in case of lymphosarcoma RLS-40. Thus, the recombinant vaccinia virus LIVP-GFP is able to inhibit the growth of malignant cells with the MDR phenotype and tumour metastasis when administered in the early stages of tumour development.

KeywordsMultiple drug resistance Vaccinia virus Cancer Human and murine cancer cells Melanoma B16 Oncolytic action Virotherapy Interleukin IL-6 Immunotherapy Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-1002-x contains supplementary material, which is available to authorized users.

An erratum to this article can be found at http:-dx.doi.org-10.1186-s12967-016-1041-3.

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Autor: Elena P. Goncharova - Julia S. Ruzhenkova - Ivan S. Petrov - Sergey N. Shchelkunov - Marina A. Zenkova

Fuente: https://link.springer.com/







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